The vif protein is likely to play an essential role during natural infections by HIV-1 and other lentiviruses. Vif is a critical determinant of virus infectivity. The biological function of vif and its mechanism of action are unknown. We have shown that vif enhances viral infectivity during virus production. We have also demonstrated that the effect of vif is associated with altered processing conformation of the HIV-1 envelope glycoproteins. The aim of this proposal is to determine role of vif in virus transmission and to elucidate its mechanism of action. The effect of vif on the conformation, processing, transport, and assembly of the envelope and gag proteins will be examined to determine the effects of vif during virus production. The effect of vif on the efficiency of virus entry and reverse transcription will be examined to elucidate why virus produced in the presence of vif is more easily transmitted. The subcellular localization of vif will be examined since the localization of vif in the host cell is likely to yield insights into its function. The effects of inhibitors of protein processing and transport will be investigated to elucidate intracellular events and virus host-cell interactions which affect viral infectivity during virus production. It is anticipated that understanding the function of vif will lead to insights into mechanisms which are critical for the transmission of HIV-1 and other lentiviruses and may lead to the development of therapeutic strategies which could inhibit virus transmission.